In vivo and in vitro investigations on the biological activity of NGF propetide (ProPEPNGF), and its role in the regulation of NGF receptor-mediated actions (DSB.AD004.192)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Istituto di Biochimica e Biologia Cellulare (IBBC)

Project manager

PAOLA TIRASSA
Phone number: 0690091307
Email: fabio.mammano@cnr.it

Abstract

Increasing evidence demonstrates that the balance between NGF receptors and their ligands regulate survival, proliferation, and differentiation of neuronal and non-neuronal cells in different tissues and organs, including eye and brain. Apoptosis, impairment of cell proliferation and migration, as well as altered differentiation of cell precursors have been indeed reported as a consequence of defective NGF signalling in different pathological conditions including neurodegenerative diseases and cancers, further supporting the biological value of NGF homeostasis. The formation of a p75NTR full length (p75NTRFL)/sortilin complex induced by proNGF binding is largely described as the most prominent pro-apoptotic effect mediating degeneration, but less it is known about the functions of p75NGF cleavage fragments, and propetides derived by proNGF processing (ProPEPNGF). We proposes that proteolytic cleavage of neurotrophin precursors and p75NTR might occur concomitantly but also in an interdependent manner in different cells/tissues, thus determining diverse contextual responses to mature NGF and proNGF, as well as to ProPEPNGF. The possibility that one or more SorCS-like co-receptors for

Goals

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Start date of activity

01/04/2018

Keywords

NGF, cell survival, p75NTR

Last update: 02/05/2025